DESCRIPTION (Adapted from applicant's abstract and specific aims): Since the discovery of natriuretic peptides in 1981, a tremendous amount of research has characterized the molecular biology, pharmacology, and physiologic significance of this family of peptides. At the present time, 3 main NPs are known to exist; atrial (ANP), brain (BNP) and C-type natriuretic peptides (CNP). Three NP receptors have also been characterized, the A and B receptors that are linked to particulate guanylate cyclase, and the C-receptor that is thought to serve mainly a clearance function. The peptides are thought to play a role in blood pressure and fluid homeostasis. In recent years, considerable evidence has also accrued to support the hypothesis that ANP plays a physiologic role in the regulation of pulmonary vascular tone and remodeling by ANP. This project aims to further investigate the role and mechanisms of action of the NPs and their receptors in the regulation of pulmonary vascular tone and remodeling. The specific aims are to: 1) assess the physiologic significance of NPs in modulating chronic pulmonary hypertension; 2) evaluate the mechanisms contributing to the synthesis and release of CNP and the potential physiologic role of CNP in the pulmonary vasculature; and 3) investigate regulation of NP receptor quantity, distribution, and recycling in the lungs.